1. Field of the Invention
This invention relates to compositions and methods for the inhibition of deoxyhypusine synthase, and for the growth inhibition of mammalian cells. More particularly, this invention relates to the administration of mono- and bis-guanyl diamines and polyamines.
2. Description of the Background Art
Malignant diseases are characterized by tumorigenic or neoplastic cell growth. These diseases include malignant hematological systemic diseases, carcinomas, sarcomas, myelomas, melanomas, lymphomas, papillomas, and the like. For example, malignant diseases that can be treated with deoxyhypusine synthase inhibitors include hyperplastic diseases, such as psoriasis, polyposis, hemangiomas, warts, Cushing's disease, goiter, and the like. (See, e.g., V. T. DeVita, Jr., et al., Cancer: Principles & Practice of Oncology, 2nd Ed., J. B. Lippincott Co. (1985)). Non-malignant neoplastic diseases are characterized by an undesirable proliferation of cells which is localized to the site of origin, such as benign growths. The transformation of normal cells within the body into either malignant or non-malignant neoplasms may be induced by chemical carcinogens, radiation, physical agents, or spontaneous tumorigenic growth.
The precise etiology of many malignant and nonmalignant diseases remains unknown. Accordingly, treatments for these diseases are limited, and effective agents are not always consistently available for a specific disease. These diseases have been treated, for example, by surgical techniques or by non-surgical methods, including chemotherapy, radiation, and immunotherapy. Any value of such treatment techniques, however, is often diminished by adverse side effects or risks attendant with their use. For example, non-surgical techniques such as chemotherapy generally have immunosuppressant effects and may increase the patient's susceptibility to secondary infections. Surgical treatments to excise malignant or nonmalignant tumors involve risks which accompany any invasive procedure and may not effectively remove or eliminate the entire transformed cell population. Moreover, certain malignant diseases are resistant to conventional treatment techniques. For example, most skin melanomas are considered to be radio-resistant.
To date, therefore, conventional methods and therapeutic agents have not proved to be effective or reliable for the treatment of malignant diseases and cell proliferation. For these reasons it would be desirable to provide improved methods which avoid the disadvantages of conventional agents and methods while providing effective and reliable results. Cells that are prevented from forming new proteins as a result of the inhibition of hypusine synthesis in the eukaryotic translation initiation factor 5A are not able to proliferate. Therefore, the inhibition of this amino acid's formation can provide novel methods for the prevention of cell proliferation.